Beta-adrenergic antagonists and alpha-adrenergic agonists can reduce cardiovascular, responses to mental stress. Mounting evidence suggests these drugs act in the central nervous system to reduce sympathetic neural outflow. Using direct intraneural recordings (microneurography), I propose to 1) identify neural mechanisms regulating sympathetic responses to stress and 2) compare skin and muscle sympathetic stress responses in borderline hypertensives and normotensives. First: In animals, central beta-2 adrenergic receptor blockade reduces sympathetic outflow during stress. I have shown that acute administration of propranolol (a central and peripheral beta-1 and beta-2 antagonist) reduces sympathetic nerve responses to stress in humans. I will determine the influence of centrally and peripherally acting beta antagonists, and of beta-1 and beta-2 receptor antagonists, on the regulation of sympathetic neural outflow during stress. Second: Acutely, propranolol increases resting sympathetic outflow. Resting sympathetic outflow declines with chronic administration. This may reflect resetting of central or peripheral mechanisms with chronic administration. It is not known whether chronic propranolol administration suppresses sympathetic outflow during stress. I will determine whether chronic beta antagonist administration suppresses sympathetic nerve responses to stress. Third: In animals, centrally administered alpha-2 agonists reduce sympathetic outflow during stress. In humans, alpha-2 agonists reduce plasma norepinephrine responses to stress. This may reflect reduced sympathetic outflow or peripheral effects (e.g., prejunctional modulation of norepinephrine release). I will determine whether an alpha-2 agonist reduces sympathetic nerve responses to stress. Fourth: Mental stress may play a role in the development of hypertension. Recent research has focused on the cardiovascular responses to stress in those at risk for hypertension. For example, there is evidence that borderline hypertensives have exaggerated blood pressure responses to stress. It is not known whether these responses reflect enhanced central sympathetic outflow. I will determine whether sympathetic outflow to muscle and skin during stress is greater in borderline hypertensive vs normotensive individuals.